title: Hematopoietic stem cell expansion caused by a synthetic fragment of leptin.
abstract: Leptin is a cytokine that regulates food intake, energy expenditure and hematopoiesis. Based on the tridimensional structure of the human leptin molecule, six fragments have been synthesized, (Ac-Lep23-47-NH2, [LEP1]; Ac-Lep48-71-NH2, [LEP2]; Ac-Lep72-88-NH2, [LEP3]; Ac-Lep92-115-NH2, [LEP4], Ac-[Ser(117)]-Lep116-140-NH2, [LEP5] and Ac-Lep141-164-NH2, [LEP6]), and their effects on hematopoiesis were evaluated. The mice were treated with 1mg/kg LEP5 for 3 days. The mature and primitive hematopoietic populations were quantified. We observed that the mature populations from the bone marrow and spleen were not affected by LEP5. However, the peptide caused at least a two-fold increase in the number of hematopoietic stem cells, the most primitive population of the bone marrow. Additionally, the number of granulocyte/macrophage colony-forming units produced by bone marrow cells in methylcellulose also increased by 40% after treatment with LEP5, and the leptin receptor was activated. These results show that the leptin fragment LEP5 is a positive modulator of the in vivo expansion of hematopoietic stem cells.
authors.affiliation: Departamento de Bioquímica, Universidade Federal de São Paulo, Rua Três de Maio 100, São Paulo, SP 04044-020, Brazil.
authors.forename: Carol C
authors.initials: CC
authors.lastname: Dias
authors.forename: Amanda
authors.initials: A
authors.lastname: Nogueira-Pedro
authors.forename: Christiano M V
authors.initials: CM
authors.lastname: Barbosa
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Ribeiro-Filho
authors.forename: Frederick
authors.initials: F
authors.lastname: Wasinski
authors.forename: Ronaldo C
authors.initials: RC
authors.lastname: Araújo
authors.forename: Vani Xavier
authors.initials: VX
authors.lastname: de Oliveira
authors.forename: Antonio
authors.initials: A
authors.lastname: Miranda
authors.forename: Edgar J
authors.initials: EJ
authors.lastname: Paredes-Gamero
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D054411:Receptors, Leptin / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D020738:Leptin; D010446:Peptide Fragments; D054411:Receptors, Leptin; C515447:leptin receptor, mouse